Minibeam Radiation therapy: Dosimetry, Physics, Radiobiology, and Emerging Clinical Insights

Minibeam radiotherapy (MBRT) is a form of spatially fractionated radiation therapy that uses arrays of submillimetric beamlets to generate highly heterogeneous dose distributions composed of alternating high-dose peaks and low-dose valleys. A growing body of preclinical evidence demonstrates that MBRT can maintain, and in some cases improve, tumor control while markedly reducing normal tissue toxicity. Beyond its physical characteristics, MBRT induces distinct biological responses, including vascular modulation, immune activation, redox signaling, and intercellular communication, supporting its characterization as a biologically distinct irradiation paradigm rather than a simple dosimetric optimization strategy. Despite these promising findings, important challenges remain for mainstream clinical implementation. Conventional dosimetry protocols and treatment planning systems are not designed to resolve submillimetric dose patterns, requiring high-resolution detectors, biologically meaningful dose metrics, and Monte Carlo-based planning approaches. In addition, inconsistent definitions of key parameters such as peak dose, valley dose, and peak-to-valley dose ratio (PVDR) limit reproducibility and comparison across studies. Considerations related to motion and delivery accuracy may also become relevant in certain applications, particularly for extracranial treatments, where preservation of the intended spatial dose modulation may influence therapeutic outcomes. Recent veterinary studies, early human applications, and expanding preclinical evidence continue to support MBRT as a promising strategy for widening the therapeutic window of radiotherapy.